New Catalytic Methods for the Synthesis of Biomedically Relevant Carbohydrates

项目总结/摘要 碳水化合物（也称为多糖或聚糖）在生物分子中占据中心作用， 它们参与了生物学中的许多信号和识别过程。此外，委员会认为， 碳水化合物是许多疫苗、抗糖尿病疫苗和抗病毒疫苗的基本结构成分 药物和抗肿瘤候选药物。尽管在化学糖基化方法方面取得了重大进展， 提供精确控制糖苷键的异头构型的一般技术是 需求在这项提案中，我们的目标是开发有效和实用的合成方法和策略 生物活性低聚糖。在目标1中，我们将扩展亲核糖基供体的工具集。在Aim中 2、我们将开发和应用氧化糖基化法制备低聚糖， 定义的异头构型。这种新颖的方法将建立一个强大的协议， 异头键的构型在亲核糖基供体的构型中预定义， 是独立于碳水化合物链的结构，保护基团，和醇受体。 这种方法，结合C-糖基化，将解决寡糖的关键挑战 合成，并且可以并入自动化和高通量合成中。鉴于一般性 和糖基化步骤的可预测性，研究人员可以使用这项新技术， 最低限度的有机合成培训，这项研究的发现可能会对有机合成产生重要影响。 开发新的诊断工具和治疗方法。

PROJECT SUMMARY/ABSTRACT Carbohydrates (also known as saccharides or glycans) occupy a central role among biomolecules due to their participation in a number of signaling and recognition processes in biology. Moreover, carbohydrates are essential structural components of numerous vaccines, anti-diabetic and anti-viral drugs, and anti-tumor drug candidates. Despite significant advances in chemical glycosylation methods, general technologies which offer a precise control of anomeric configuration of the glycosidic bond are in demand. In this proposal we aim to develop methods and strategies for efficient and practical synthesis of bioactive oligosaccharides. In Aim 1, we will expand the toolset of nucleophilic glycosyl donors. In Aim 2, we will develop and apply oxidative glycosylation method for the preparation of oligosaccharides with defined anomeric configuration. This novel method will establish a robust protocol for which the configuration of the anomeric bond is pre-defined in the configuration of nucleophilic glycosyl donor and is independent from the structure of the carbohydrate chain, protective groups, and alcohol acceptors. This method, in combination with C-glycosylation, will address the critical challenges of oligosaccharides synthesis and can be incorporated into automated and high-throughput synthesis. Given the generality and a predictable nature of the glycosylation step, this new technology can be used by researchers with minimal training in organic synthesis, and the discoveries of this study can have important impact on the development of new diagnostic tools and therapies.